The inotropic medication milrinone (Coritrope) has little effect on heart rate. Patients who have recently developed acute decompensated heart failure receive it as a short-term treatment.

Milrinone Uses:

• Inotropic support in heart failure:

  • It is meant to treat acutely decompensated heart failure with short-term intravenous treatment (HF)
  • Guideline recommendations:
    • Heart failure: 
      • Bridge therapy may be beneficial for individuals awaiting a heart transplant or mechanical circulatory support when stage  DHF is resistant to GMDT and device therapy.
      • Long-term care should be provided to a select group of stage D HF patients who are unsuitable for mechanical circulatory  support or a heart transplant and who are resistant to drug and device treatment (palliative therapy).
      • Hospitalised patients' need short-term care when they have severe systolic dysfunction, low blood pressure, and  dramatically reduced cardiac output

• Off Label Use of Milrinone in Adults:

  • Bridge to heart transplantation
  • Cardiogenic shock
  • Symptom relief in advanced heart failure
  • Postoperative inotropic support for heart transplant recipients

Milrinone Dose in Adults:

Milrinone (Coritrope) Dose in heart failure (As an inotropic drug):

• Intravenous:
  • Loading dose: The 2013 ACCF/AHA heart failure recommendations do not advocate giving 50 mcg/kg over 10 minutes, however, it is possible.
  • Maintenance dose: Lower starting dosages of 0.1 mcg/kg/minute for IV infusions have also been suggested, with final maintenance doses of 0.2–0.3 mcg/kg/minute.The 2013 ACCF/AHA heart failure guidelines advise using a maintenance dosage of 0.125 to 0.75 mcg/kg/minute.
  • Dosage titration based on response

Note: Infusion at a starting dose of 0.5 mcg/kg/minute causes significant hemodynamic changes to be observed at 30 minutes, similar effects on pulmonary capillary wedge  pressure, and cardiac index to be observed at 2 and 3 hours, respectively, when compared to a loading dosage regimen.

Milrinone (Coritrope) Dose in the Bridge to heart transplantation (off-label):

• 0.1 to 0.75 mcg/kg/minute intravenously; adjust the dosage to best meet clinical needs.

Milrinone (Coritrope) Dose in the treatment of Cardiogenic shock (off-label):

• Intravenous: 0.125 - 0.75 mcg/kg/minute

Milrinone (Coritrope) Dosage for Off-Label Postoperative Inotropic Support in Heart Transplant Recipients:

• During the first three to five days, wean as tolerated while administering an IV dosage of 0.375 to 0.75 mcg/kg/minute at the lowest effective dose.

Milrinone Dose in Children:

Dose of milrinone (Coritrope) for hemodynamic support in cases of cardiogenic shock, septic shock, or acute decompensated heart failure There is no established optimal dosage:

Key point: Given that inter-patient variability in clearance may exist, whether or not a patient has low cardiac output syndrome or an acute renal injury, individualized dosage and titration to effect should be employed.

• Newborns, Children, and Adolescents: IV, Intraosseous:

  • 50 mcg/kg of a loading dose can be given during a 10- to 60-minute period.

  • Continuous IV or intraosseous infusion after the loading dose; infusion dosage range: 0.25 to 0.75 mcg/kg/minute; titrate dose as needed

  • Some facilities don't use a loading dosage because of the possibility of hypotension

Low cardiac output syndrome (LCOS) prevention after CHD corrective surgery with milrinone (Coritrope) dosage:

• Infants and Children: IV:

  • Maintenance dose: a 0.25 or 0.75 mcg/kg/minute continuous intravenous infusion.

  • According to a study, high dose milrinone (loading dose: 75 mcg/kg, continuous infusion: 0.75 mcg/kg/minute) has a relative reduction of 64 percent for the development of LCOS, while low dose milrinone group (loading dose: 25 mcg/kg/minute, continuous infusion: 0.25 mg/kg/minute) was statistically insignificant for reducing the development of LCOS.

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  • Loading dose: 25 or 75 mcg/kg infused over 60 minutes

Pregnancy Risk Factor C

• No negative outcomes have been found in studies on animal reproduction. Studies do, however, indicate higher resorption.

Use during breastfeeding:

• If Milrinone is found in breast milk is unknown.
• It is recommended that it be used with caution by lactating mothers

Milrinone (Coritrope) Dose in Kidney Disease:

• Manufacturer recommended adjustment:

  • CrCl 5 mL/minute/1.73 m : Administer 0.2 mcg/kg/minute
  • CrCl 20 mL/minute/ 1.73 m : Administer 0.28 mcg/kg/minute
  • CrCl 50 mL/minute/1.73 m : Administer 0.43 mcg/kg/minute
  • CrCl 30 mL/minute/1.73 m : Administer 0.33 mcg/kg/minute
  • CrCl 10 mL/minute/1.73 m : Administer 0.23 mcg/kg/minute
  • CrCl 40 mL/minute/1.73 m : Administer 0.38 mcg/kg/minute

• Alternative Dosage Modifications for Patients with Renal Impairment

Dose in Liver disease:

The manufacturer has not provided any dose adjustment.

Side Effects of Milrinone (Coritrope):

• Cardiovascular:

  • Hypotension
  • Ventricular arrhythmia
  • Supraventricular cardiac arrhythmia
  • Chest pain
  • Angina pectoris

• Central nervous system:

  • Headache

Contraindications to Milrinone (Coritrope):

• Hypersensitivity to any component of the formula

Warnings and precautions

• Arrhythmias:

  • There are two types of arrhythmia: supraventricular tachycardia (with milrinone) and Ventricular Tachycardia (with milrinone).
  • Pay attention; sudden cardiac death has been observed.
  • An extended half-life may be experienced by patients with compromised renal function. Even after discontinuing milrinone, arrhythmias can still happen.
  • Before you start the therapy or dosing escalation, ensure that the patient is free from atrial fibrillation.
  • Install appropriate safeguards to guard heart transplant patients against sudden cardiac death.

• Hypotension

  • Milrinone can cause hypotension. Monitor your BP often
  • Temporary dose reductions or discontinuations may be necessary

• Cardiovascular disease

  • If the patient is suffering from severe obstructive or pulmonic valve disease, do not use. Instead, seek surgical relief.
  • Milrinone could increase the obstruction of the outflow tract in hypertrophic cardiomyopathy

• Electrolyte imbalance:

  • Arrhythmias can be caused by electrolyte imbalances, especially hypokalaemia and hypomagnesemia. If you notice an imbalance, correct it before using

• Renal impairment

  • Reduce the infusion rate if you have renal impairment.
  • Milrinone's half-life prolongs with renal impairment. Longer hypotension could occur.

Milrinone: Drug Interaction

Monitoring parameters:

• Platelet count
• Heart rate
• Infusion site
• Fluid status
• Renal function
• ECG
• Electrolytes (especially potassium and magnesium)
• Blood pressure

Monitor the following values if a pulmonary artery catheter is in place.

• Pulmonary capillary wedge pressure
• Systemic vascular resistance
• Cardiac index
• Pulmonary vascular resistance.
• Stroke volume

Consult the regulations and approaches of each specific institution.

How to administer Milrinone (Coritrope)?

Intravenous (only):

• Undiluted loading dosage (optional) should be administered gradually over a 10-minute period; seeing the injection rate may be made easier by dilution to a total volume that is rounded to 10 or 20 mL.
• Utilize a continuous infusion pump to administer the maintenance dosage.

Mechanism of action of Milrinone (Coritrope):

• A selective phosphodiesterase inhibitor called milrinone causes vasodilation by acting on the heart and vascular tissue.
• It also produces little chronotropic activity.

Metabolism:

• Hepatic (minor); majority remains metabolized

The onset of action:

• IV: 5 - 15 minutes

Excretion:

• Urine (83 percent as unchanged drug; 12 percent as 0-glucuronide metabolite)
• A significant method of milrinone removal is active tubular secretion.

Protein binding,

• plasma: ~70%

Half-life elimination:

• Infants (after cardiac surgery): 3.15 ± 2 hours
• Children (after cardiac surgery): 1.86 ± 2 hours
• Adults:
  • Heart failure: 2.3–2.4 hours; individuals with renal dysfunction have a longer half-life.
  • Continuous venovenous hemofiltration (CVVH) for severe heart failure: 20.1 3.3 hours

International Brand Names of Milrinone:

• Coritrope
• Corotrop
• Corotrope
• Inovad
• Lunan Likang
• Milicor
• Milron
• Nefrisol
• Primacor
• Unacor

Milrinone Brand Names in Pakistan: